Identification

Name
Felodipine
Accession Number
DB01023  (APRD00374)
Type
Small Molecule
Groups
Approved, Investigational
Description

Felodipine is a long-acting 1,4-dihydropyridine calcium channel blocker (CCB)b. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, felodipine prevents calcium-dependent myocyte contraction and vasoconstriction. Felodipine is the most potent CCB in use and is unique in that it exhibits fluorescent activity. In addition to binding to L-type calcium channels, felodipine binds to a number of calcium-binding proteins, exhibits competitive antagonism of the mineralcorticoid receptor, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and blocks calcium influx through voltage-gated T-type calcium channels. Felodipine is used to treat mild to moderate essential hypertension.

Structure
Thumb
Synonyms
  • (±)-ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate
  • 3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate
  • 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid ethyl methyl ester
  • Felodipina
  • Felodipine
  • Felodipino
  • Felodipinum
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FelodipineTablet, extended release10 mg/1OralMed Pharma Co., Ltd.2011-06-072012-05-15Us
FelodipineTablet, extended release5 mg/1OralMed Pharma Co., Ltd.2011-06-072012-05-15Us
FelodipineTablet, extended release2.5 mg/1OralMed Pharma Co., Ltd.2011-06-072012-05-15Us
Felodipineextended-release TabletsTablet, extended release10 mg/1OralRanbaxy Inc.2008-09-10Not applicableUs
Felodipineextended-release TabletsTablet, extended release5 mg/1OralRanbaxy Inc.2008-09-10Not applicableUs
Felodipineextended-release TabletsTablet, extended release2.5 mg/1OralRanbaxy Inc.2008-09-10Not applicableUs
PlendilTablet, extended release10 mg/1OralAstra Zeneca Lp1991-09-162011-12-31Us
PlendilTablet, extended release10 mg/1OralPhysicians Total Care, Inc.1991-07-252011-05-31Us
PlendilTablet, extended release5 mg/1OralAstra Zeneca Lp1991-09-162012-01-31Us
PlendilTablet, extended release5 mg/1OralPhysicians Total Care, Inc.1991-07-252011-05-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-felodipineTablet, extended release2.5 mgOralApotex Corporation2016-04-22Not applicableCanada
Apo-felodipineTablet, extended release10 mgOralApotex Corporation2016-04-22Not applicableCanada
Apo-felodipineTablet, extended release5 mgOralApotex Corporation2016-04-22Not applicableCanada
FelodipineTablet, film coated, extended release10 mg/1OralMylan Pharmaceuticals Inc.2008-04-18Not applicableUs
FelodipineTablet, extended release10 mg/1OralTorrent Pharmaceuticals Limited2011-11-28Not applicableUs13668 0134 01 nlmimage10 78403c41
FelodipineTablet, film coated, extended release5 mg/1OralJubilant Cadista Pharmaceuticals Inc.2016-08-19Not applicableUs
FelodipineTablet, film coated, extended release10 mg/1OralRichmond Pharmaceuticals2004-11-022018-11-30Us
FelodipineTablet, film coated2.5 mg/1OralPhysicians Total Care, Inc.2005-11-08Not applicableUs53489 0368 01 nlmimage10 293414c0
FelodipineTablet, film coated, extended release10 mg/1OralWockhardt2010-12-05Not applicableUs
FelodipineTablet, film coated, extended release5 mg/1Oralbryant ranch prepack2004-11-022018-05-29Us63629 159720180907 15195 w4yupq
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Altace Plus Felodipine 2.5mg + 2.5mgFelodipine (2.5 mg) + Ramipril (2.5 mg)TabletOralSanofi Aventis2006-06-272012-10-10Canada
Altace Plus Felodipine 5mg + 5mgFelodipine (5 mg) + Ramipril (5 mg)TabletOralSanofi Aventis2006-06-272012-10-15Canada
LexxelFelodipine (5 mg/1) + Enalapril maleate (5 mg/1)Tablet, extended releaseOralAstra Zeneca Lp1996-12-272010-08-31Us
International/Other Brands
Felodur ER / Felogard / Penedil / Plendil Depottab (AstraZeneca) / Plendil ER (AstraZeneca) / Plendil Retard (AstraZeneca) / Splendil
Categories
UNII
OL961R6O2C
CAS number
72509-76-3
Weight
Average: 384.254
Monoisotopic: 383.069113515
Chemical Formula
C18H19Cl2NO4
InChI Key
RZTAMFZIAATZDJ-UHFFFAOYSA-N
InChI
InChI=1S/C18H19Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8,15,21H,5H2,1-4H3
IUPAC Name
3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
CCOC(=O)C1=C(C)NC(C)=C(C1C1=C(Cl)C(Cl)=CC=C1)C(=O)OC

Pharmacology

Indication

For the treatment of mild to moderate essential hypertension.

Associated Conditions
Pharmacodynamics

Felodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells.

Mechanism of action

Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of felodipine result in an overall decrease in blood pressure. Felodipine may be used to treat mild to moderate essential hypertension.

TargetActionsOrganism
AVoltage-dependent L-type calcium channel subunit alpha-1C
inhibitor
Human
AVoltage-dependent calcium channel subunit alpha-2/delta-1
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit beta-2
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit alpha-1D
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit alpha-1S
inhibitor
Human
UVoltage-dependent T-type calcium channel subunit alpha-1H
inhibitor
Human
UVoltage-dependent calcium channel subunit alpha-2/delta-2
inhibitor
Human
UCalmodulin
other
Human
UCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
inhibitor
Human
UCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A
inhibitor
Human
UMineralocorticoid receptor
antagonist
Human
UTroponin C, skeletal muscle
other
Human
UTroponin C, slow skeletal and cardiac muscles
other
Human
Absorption

Is completely absorbed from the gastrointestinal tract; however, extensive first-pass metabolism through the portal circulation results in a low systemic availability of 15%. Bioavailability is unaffected by food.

Volume of distribution
  • 10 L/kg
Protein binding

99%, primarily to the albumin fraction.

Metabolism

Hepatic metabolism primarily via cytochrome P450 3A4. Six metabolites with no appreciable vasodilatory effects have been identified.

Route of elimination

Although higher concentrations of the metabolites are present in the plasma due to decreased urinary excretion, these are inactive. Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.

Half life

17.5-31.5 hours in hypertensive patients; 19.1-35.9 hours in elderly hypertensive patients; 8.5-19.7 in healthy volunteers.

Clearance
  • 0.8 L/min [Young healthy subjects]
Toxicity

Symptoms of overdose include excessive peripheral vasodilation with marked hypotension and possibly bradycardia. Oral rat LD50 is 1050 mg/kg.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Felodipine Metabolism PathwayDrug metabolism
Felodipine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Felodipine can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Felodipine can be decreased when combined with (S)-Warfarin.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Felodipine is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of Felodipine can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Felodipine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Felodipine.
5-androstenedioneThe metabolism of Felodipine can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Felodipine can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Felodipine can be decreased when combined with 6-O-benzylguanine.
AbafunginThe therapeutic efficacy of Abafungin can be increased when used in combination with Felodipine.
Food Interactions
  • Grapefruit down regulates post-translational expression of CYP3A4, the major metabolizing enzyme of nifedipine. Grapefruit, in all forms (e.g. whole fruit, juice and rind), can significantly increase serum levels of nifedipine and may cause toxicity. Avoid grapefruit products while on this medication.
  • Take without regard to meals.

References

Synthesis Reference

Vinay Sharma, "Preparation of micron-size felodipine particles by microfluidization." U.S. Patent US20020086061, issued July 04, 2002.

US20020086061
General References
  1. Dunselman PH, Edgar B: Felodipine clinical pharmacokinetics. Clin Pharmacokinet. 1991 Dec;21(6):418-30. [PubMed:1782737]
External Links
Human Metabolome Database
HMDB0015158
KEGG Drug
D00319
PubChem Compound
3333
PubChem Substance
46506968
ChemSpider
3216
BindingDB
189379
ChEBI
585948
ChEMBL
CHEMBL1480
Therapeutic Targets Database
DAP000487
PharmGKB
PA449591
IUPHAR
4190
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Felodipine
ATC Codes
C08CA02 — FelodipineC09BB05 — Ramipril and felodipine
AHFS Codes
  • 24:28.08 — Dihydropyridines
FDA label
Download (228 KB)
MSDS
Download (55.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentFood-Drug Interactions1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension) / High Cholesterol / Type 2 Diabetes Mellitus1
3CompletedTreatmentBMI >30 kg/m2 / High Blood Pressure (Hypertension)1
4CompletedPreventionDisorders Related to Lung Transplantation1
4CompletedTreatmentHigh Blood Pressure (Hypertension)2
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Left Ventricular Hypertrophy1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension) / Sexual Dysfunctions1
Not AvailableCompletedNot AvailableHealthy Volunteers2
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableUnknown StatusBasic ScienceHigh Blood Pressure (Hypertension) / Insulin Resistance / Microcirculation1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • A-S Medication Solutions LLC
  • AstraZeneca Inc.
  • Atlantic Biologicals Corporation
  • Bryant Ranch Prepack
  • Cardinal Health
  • Heartland Repack Services LLC
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Ranbaxy Laboratories
  • Resource Optimization and Innovation LLC
  • Richmond Pharmacy
  • Sandhills Packaging Inc.
  • UDL Laboratories
  • Va Cmop Dallas
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
TabletOral
Tablet, film coatedOral2.5 mg/1
Tablet, film coated, extended releaseOral10 mg/1
Tablet, film coated, extended releaseOral2.5 mg/1
Tablet, film coated, extended releaseOral5 mg/1
Tablet, extended releaseOral10 mg/1
Tablet, extended releaseOral2.5 mg/1
Tablet, extended releaseOral5 mg/1
Tablet, extended releaseOral
Tablet, extended releaseOral10 mg
Tablet, extended releaseOral2.5 mg
Tablet, extended releaseOral5 mg
Prices
Unit descriptionCostUnit
Plendil 10 mg 24 Hour tablet3.17USD tablet
Plendil er 10 mg tablet3.05USD tablet
Plendil 10 mg tablet sa2.96USD tablet
Felodipine 10 mg 24 Hour tablet2.95USD tablet
Plendil er 2.5 mg tablet2.94USD tablet
Felodipine er 10 mg tablet2.72USD tablet
Plendil er 5 mg tablet2.6USD tablet
Plendil 5 mg 24 Hour tablet1.77USD tablet
Plendil 2.5 mg 24 Hour tablet1.76USD tablet
Felodipine 5 mg 24 Hour tablet1.67USD tablet
Plendil 2.5 mg tablet sa1.65USD tablet
Plendil 5 mg tablet sa1.65USD tablet
Felodipine 2.5 mg 24 Hour tablet1.57USD tablet
Felodipine er 2.5 mg tablet1.51USD tablet
Felodipine er 5 mg tablet1.51USD tablet
Renedil 10 mg Extended-Release Tablet1.22USD tablet
Plendil 10 mg Extended-Release Tablet1.15USD tablet
Renedil 5 mg Extended-Release Tablet0.81USD tablet
Plendil 5 mg Extended-Release Tablet0.77USD tablet
Sandoz Felodipine 10 mg Extended-Release Tablet0.73USD tablet
Renedil 2.5 mg Extended-Release Tablet0.6USD tablet
Plendil 2.5 mg Extended-Release Tablet0.57USD tablet
Sandoz Felodipine 5 mg Extended-Release Tablet0.48USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)145 °CNot Available
water solubility19.7 mg/LNot Available
logP3.86SANGSTER (1994)
Caco2 permeability-4.64ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.00715 mg/mLALOGPS
logP4.36ALOGPS
logP3.44ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)19.46ChemAxon
pKa (Strongest Basic)-6.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area64.63 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity99.2 m3·mol-1ChemAxon
Polarizability37.96 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9878
Blood Brain Barrier-0.83
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.5149
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterNon-inhibitor0.8664
CYP450 2C9 substrateNon-substrate0.8357
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6954
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorInhibitor0.8948
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9304
Ames testNon AMES toxic0.7849
CarcinogenicityNon-carcinogens0.7511
BiodegradationNot ready biodegradable0.9527
Rat acute toxicity2.4526 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9455
hERG inhibition (predictor II)Non-inhibitor0.8734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udu-0139000000-085071c20c5d0c134d8f

Taxonomy

Description
This compound belongs to the class of organic compounds known as dihydropyridinecarboxylic acids and derivatives. These are compounds containing a dihydropyridine moiety bearing a carboxylic acid group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Hydropyridines
Direct Parent
Dihydropyridinecarboxylic acids and derivatives
Alternative Parents
Dichlorobenzenes / Dicarboxylic acids and derivatives / Aryl chlorides / Vinylogous amides / Methyl esters / Enoate esters / Amino acids and derivatives / Enamines / Dialkylamines / Azacyclic compounds
show 5 more
Substituents
Dihydropyridinecarboxylic acid derivative / 1,2-dichlorobenzene / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Dicarboxylic acid or derivatives / Benzenoid / Vinylogous amide
show 22 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
ethyl ester, dichlorobenzene, methyl ester, dihydropyridine (CHEBI:585948)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1C
Uniprot ID
Q13936
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1C
Molecular Weight
248974.1 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [PubMed:10525060]
  3. Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. [PubMed:17475903]
  4. Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-...
Gene Name
CACNA2D1
Uniprot ID
P54289
Uniprot Name
Voltage-dependent calcium channel subunit alpha-2/delta-1
Molecular Weight
124566.93 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [PubMed:10525060]
  3. Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. [PubMed:17475903]
  4. Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and ina...
Gene Name
CACNB2
Uniprot ID
Q08289
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-2
Molecular Weight
73579.925 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [PubMed:10525060]
  3. Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. [PubMed:17475903]
  4. Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity involved sa node cell action potential
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1D
Uniprot ID
Q01668
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1D
Molecular Weight
245138.75 Da
References
  1. Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. doi: 10.1124/mol.108.049981. Epub 2008 Nov 24. [PubMed:19029287]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1S
Uniprot ID
Q13698
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1S
Molecular Weight
212348.1 Da
References
  1. Peterson BZ, Catterall WA: Allosteric interactions required for high-affinity binding of dihydropyridine antagonists to Ca(V)1.1 Channels are modulated by calcium in the pore. Mol Pharmacol. 2006 Aug;70(2):667-75. Epub 2006 May 4. [PubMed:16675661]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Scaffold protein binding
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1H
Uniprot ID
O95180
Uniprot Name
Voltage-dependent T-type calcium channel subunit alpha-1H
Molecular Weight
259160.2 Da
References
  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [PubMed:1281221]
  2. Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30. [PubMed:18974361]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-t...
Gene Name
CACNA2D2
Uniprot ID
Q9NY47
Uniprot Name
Voltage-dependent calcium channel subunit alpha-2/delta-2
Molecular Weight
129816.095 Da
References
  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [PubMed:1281221]
  2. Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30. [PubMed:18974361]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other
General Function
Titin binding
Specific Function
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number...
Gene Name
CALM1
Uniprot ID
P0DP23
Uniprot Name
Calmodulin
Molecular Weight
16837.47 Da
References
  1. Bostrom SL, Westerlund C, Rochester S, Vogel HJ: Binding of a dihydropyridine felodipine-analogue to calmodulin and related calcium-binding proteins. Biochem Pharmacol. 1988 Oct 1;37(19):3723-8. [PubMed:3178884]
  2. Johnson JD, Andrews CT, Khabbaza EJ, Mills JS: The interaction of felodipine with calcium-binding proteins. J Cardiovasc Pharmacol. 1987;10 Suppl 1:S53-9. [PubMed:2442519]
  3. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041]
  4. Lamers JM, Verdouw PD, Mas-Oliva J: The effects of felodipine and bepridil on calcium-stimulated calmodulin binding and calcium pumping ATPase of cardiac sarcolemma before and after removal of endogenous calmodulin. Mol Cell Biochem. 1987 Dec;78(2):169-76. [PubMed:2964559]
  5. Mills JS, Bailey BL, Johnson JD: Cooperativity among calmodulin's drug binding sites. Biochemistry. 1985 Aug 27;24(18):4897-902. [PubMed:4074665]
  6. Walsh MP, Sutherland C, Scott-Woo GC: Effects of felodipine (a dihydropyridine calcium channel blocker) and analogues on calmodulin-dependent enzymes. Biochem Pharmacol. 1988 Apr 15;37(8):1569-80. [PubMed:2833901]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a preference for cGMP as...
Gene Name
PDE1B
Uniprot ID
Q01064
Uniprot Name
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
Molecular Weight
61379.235 Da
References
  1. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041]
  2. Sharma RK, Wang JH, Wu Z: Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists. J Neurochem. 1997 Aug;69(2):845-50. [PubMed:9231746]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a higher affinity for cG...
Gene Name
PDE1A
Uniprot ID
P54750
Uniprot Name
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A
Molecular Weight
61251.38 Da
References
  1. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041]
  2. Sharma RK, Wang JH, Wu Z: Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists. J Neurochem. 1997 Aug;69(2):845-50. [PubMed:9231746]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates targ...
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
Molecular Weight
107066.575 Da
References
  1. Dietz JD, Du S, Bolten CW, Payne MA, Xia C, Blinn JR, Funder JW, Hu X: A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension. 2008 Mar;51(3):742-8. doi: 10.1161/HYPERTENSIONAHA.107.103580. Epub 2008 Feb 4. [PubMed:18250364]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other
General Function
Calcium ion binding
Specific Function
Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site fo...
Gene Name
TNNC2
Uniprot ID
P02585
Uniprot Name
Troponin C, skeletal muscle
Molecular Weight
18121.895 Da
References
  1. Bostrom SL, Westerlund C, Rochester S, Vogel HJ: Binding of a dihydropyridine felodipine-analogue to calmodulin and related calcium-binding proteins. Biochem Pharmacol. 1988 Oct 1;37(19):3723-8. [PubMed:3178884]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other
General Function
Troponin t binding
Specific Function
Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site fo...
Gene Name
TNNC1
Uniprot ID
P63316
Uniprot Name
Troponin C, slow skeletal and cardiac muscles
Molecular Weight
18402.36 Da
References
  1. Bostrom SL, Westerlund C, Rochester S, Vogel HJ: Binding of a dihydropyridine felodipine-analogue to calmodulin and related calcium-binding proteins. Biochem Pharmacol. 1988 Oct 1;37(19):3723-8. [PubMed:3178884]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. [PubMed:12433827]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Schoch GA, Yano JK, Sansen S, Dansette PM, Stout CD, Johnson EF: Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid. J Biol Chem. 2008 Jun 20;283(25):17227-37. doi: 10.1074/jbc.M802180200. Epub 2008 Apr 15. [PubMed:18413310]
  2. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Enzyme inhibition data obtained from an in vitro study using felodipine at supratherapeutic concentrations.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Ma B, Prueksaritanont T, Lin JH: Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30. [PubMed:10640508]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Ma B, Prueksaritanont T, Lin JH: Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30. [PubMed:10640508]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [PubMed:11716514]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 13:32